Overview

Also Known As:Pms2-

This targeted mutation of the postmeiotic segregation increased 2 gene (Pms2) exhibits male infertility, microsatellite DNA instability and increased tumor incidence. This strain may useful in the studies of spermatogenesis, cancer and DNA mismatch repair.

Donating Investigator

Dr. R. M. Liskay, Oregon Health Sciences University

Genetic overview

Genetic Background	Generation

Pms2^tm1Lisk

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Pms2	PMS1 homolog2, mismatch repair system component

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Research Applications

Cancer Research
Reproductive Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice that are homozygous for the targeted mutation are viable, but show an increased incidence of sarcomas and lymphomas. Sperm, tail and tumor cells from homozygous mice exhibit microsatellite instability. Male mice on the mixed C57BL/6 and 129S2 background are infertile with reduced numbers of spermatozoa. Spermatozoa exhibit misshapen heads, truncated, irregular flagella. This strain may be useful in the studies of spermatogenesis, cancer and DNA mismatch repair.

Development

A targeting vector was designed to replace exon 2 of the targeted gene with a neomycin resistance cassette. The construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts, and chimeric males were bred to C57BL/6 females. Heterozygous offspring were bred to C57BL/6 mice for greater than 10 generations prior to arrival at The Jackson Laboratory.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Baker SM; Bronner CE; Zhang L; Plug AW; Robatzek M; Warren G; Elliott EA; Yu J; Ashley T; Arnheim N; Flavell RA; Liskay RM. 1995. Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis. Cell 82(2):309-19PubMed: 7628019 MGI: J:27389

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Genetics

Pms2^tm1Lisk

Allele Symbol: Pms2^tm1Lisk

Allele Name	targeted mutation 1, Michael Liskay
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Pms2^-
Gene Symbol and Name	Pms2, PMS1 homolog2, mismatch repair system component
Gene Synonym(s)
Strain of Origin	129S2/SvPas
Chromosome	5
Molecular Note	A neomycin cassette was inserted into exon 2, replacing a highly conserved region of the gene. Protein was not detectable by Western analysis in fibroblast cultures from homozygous mutant animals.
Mutations Made By	Dr. Sean Baker, Oregon Health Sciences University

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Cancer Research
- Increased Tumor Incidence
  - Lymphomas
  - Other Tissues/Organs
  - Other Tissues/Organs: multiple
- Other
  - DNA Repair
Reproductive Biology Research
- Fertility Defects
  - males only

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Pms2^tm1Lisk/Pms2⁺
involves: 129S2/SvPas

homeostasis/metabolism phenotype

increased incidence of tumors by chemical induction
- Normal - however, the incidence of induced thymic lymphomas is normal
- N-methyl-N-nitrosourea (MNU)-treated mice exhibit a higher incidence and multiplicity of intestinal tumors (adenomas and adenocarcinomas) compared with similarly treated wild-type mice without loss of the wild-type allele

neoplasm

increased incidence of tumors by chemical induction
- Normal - however, the incidence of induced thymic lymphomas is normal
- N-methyl-N-nitrosourea (MNU)-treated mice exhibit a higher incidence and multiplicity of intestinal tumors (adenomas and adenocarcinomas) compared with similarly treated wild-type mice without loss of the wild-type allele

Genotype: Pms2^tm1Lisk/Pms2^tm1Lisk
involves: 129S2/SvPas * C57BL/6

reproductive system phenotype

male infertility
- female mice are fertile

oligozoospermia
- spermatozoan content of the epididymis was <25% that of wild-type

abnormal male meiosis
- abnormalities in chromosomal synapsis during meiotic prophase I

globozoospermia
- misshaped heads

abnormal sperm flagellum morphology
- truncated, irregular flagella

cellular phenotype

oligozoospermia
- spermatozoan content of the epididymis was <25% that of wild-type

abnormal mismatch repair
- DNA from tumors and sperm exhibits increased microsatellite instability

abnormal sperm flagellum morphology
- truncated, irregular flagella

globozoospermia
- misshaped heads

homeostasis/metabolism phenotype

abnormal mismatch repair
- DNA from tumors and sperm exhibits increased microsatellite instability

neoplasm

increased sarcoma incidence

increased lymphoma incidence

Genotype: Pms2^tm1Lisk/Pms2^tm1Lisk
involves: 129S2/SvPas

cellular phenotype

teratozoospermia
- mature sperm have misshapen heads and truncated or coiled flagella

abnormal mismatch repair
- absence of MMR in MEFs

chromosomal instability
- mouse embryonic fibroblasts (MEFs) exhibit in increase in microsatellite instability compared with wild-type cells
- Normal - however, telomere length is normal
- MEFs exhibit an increase in chromosome breaks, fragments, bivalent recombination figures, chromatid cross-links, chromosome fusions, and minichromosomes compared with wild-type cells
- end-to-end chromosome fusions in MEFs are slightly increased compared to in wild-type cells

coiled sperm flagellum

abnormal cell physiology
- sister chromatid exchange in mouse embryonic fibroblasts is increased compared to in wild-type cells

abnormal DNA repair
- increase in microsatellite instability and mutation frequencies

decreased male germ cell number
- severe depletion of spermatogenic cells

abnormal sperm head morphology

short sperm flagellum

endocrine/exocrine gland phenotype

abnormal seminiferous tubule morphology
- severely depleted in spermatogenic cells

small testis
- about 70% the size of wild-type testes

hematopoietic system phenotype

abnormal class switch recombination
- decrease in ex vivo class switch recombination

homeostasis/metabolism phenotype

abnormal DNA repair
- increase in microsatellite instability and mutation frequencies

abnormal mismatch repair
- absence of MMR in MEFs

immune system phenotype

abnormal class switch recombination
- decrease in ex vivo class switch recombination

mortality/aging

premature death
- median survival is reduced compared to in wild-type mice
- median survival is 13 months

neoplasm

increased B cell derived lymphoma incidence

increased carcinoma incidence

increased sarcoma incidence
- histiocytic sarcomas

increased lymphoma incidence

reproductive system phenotype

abnormal seminiferous tubule morphology
- severely depleted in spermatogenic cells

small testis
- about 70% the size of wild-type testes

decreased male germ cell number
- severe depletion of spermatogenic cells

teratozoospermia
- mature sperm have misshapen heads and truncated or coiled flagella

short sperm flagellum

coiled sperm flagellum

male infertility

abnormal sperm head morphology

References

Baker SM; Bronner CE; Zhang L; Plug AW; Robatzek M; Warren G; Elliott EA; Yu J; Ashley T; Arnheim N; Flavell RA; Liskay RM. 1995. Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis. Cell 82(2):309-19PubMed: 7628019 MGI: J:27389

Additional - Pms2^tm1Lisk related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Pms2
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as heterozygotes. Male mice homozygous for the mutation are infertile.
- Additional Breeding and Husbandry Support
Citation
When using the Pms2- mouse strain in a publication, please cite the originating article(s) and include JAX stock #010945 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Domestic Pricing for

Commercial & For-Profit

Not-For-Profit & Academic

International Pricing for

Commercial & For-Profit

Not-For-Profit & Academic

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous or wildtype for Pms2<tm1Lisk>

Related Products and Services

Frozen Mouse Embryo	B6.129S2-Pms2<tm1Lisk>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129S2-Pms2<tm1Lisk>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129S2-Pms2<tm1Lisk>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129S2-Pms2<tm1Lisk>/J Frozen Embryo	$3373.50

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a no-fee JAX Leap License prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:Pms2-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Pms2tm1Lisk

Allele Symbol: Pms2tm1Lisk

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Pms2tm1Lisk/Pms2+involves: 129S2/SvPas

homeostasis/metabolism phenotype

neoplasm

Genotype: Pms2tm1Lisk/Pms2tm1Liskinvolves: 129S2/SvPas * C57BL/6

reproductive system phenotype

cellular phenotype

homeostasis/metabolism phenotype

neoplasm

Genotype: Pms2tm1Lisk/Pms2tm1Liskinvolves: 129S2/SvPas

cellular phenotype

endocrine/exocrine gland phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

mortality/aging

neoplasm

reproductive system phenotype

References

Additional - Pms2tm1Lisk related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Pms2^tm1Lisk

Allele Symbol: Pms2^tm1Lisk

Genotype: Pms2^tm1Lisk/Pms2⁺
involves: 129S2/SvPas

Genotype: Pms2^tm1Lisk/Pms2^tm1Lisk
involves: 129S2/SvPas * C57BL/6

Genotype: Pms2^tm1Lisk/Pms2^tm1Lisk
involves: 129S2/SvPas

Additional - Pms2^tm1Lisk related